ABSTRACT

This chapter describes the effects of retinoids on squamous differentiation in normal, premalignant, and malignant epithelial tissues. Retinoids are substances structurally or functionally related to vitamin A, or retinol. The skin is the major organ where epithelial cells undergo squamous cell differentiation. Squamous cell differentiation in epidermis in vivo and in cultured keratinocytes is accompanied by the successive expression of several genes, the products of which are markers of squamous cell differentiation. Profilaggrin is a high-molecular-weight basic histidine-rich and highly phosphorylated protein that is found in keratohyaline granules present in the granular cells of keratinizing epidermis. The ability to form cross-linked envelopes is retained by many premalignant and malignant cells, which express transglutaminase and contain protein precursors for cross-linking. Cell growth is tightly linked to squamous cell differentiation in that an irreversible growth arrest is a prerequisite for the expression of squamous cell differentiation markers and terminal differentiation.